Hereditary Spastic Paraplegia (HSP) is a group of motor neuron disorders characterized by progressive lower extremity spastic weakness. Wheelchairs often required and other neurologic deficits may occur. HSP affects an estimated 20,000 individuals in the United States alone. There is no specific treatment for HSP. In May 25-27, 2000, we held the First International Symposium for HSP (ISHSP) at the Univ. Michigan. More than 50 investigators from around the world and nearly 200 clinicians, scientists, leaders of HSP support groups, and patients participated. This event served to catalyze HSP research collaborations and stimulate formation of HSP support organizations in the U.S. (Spastic Paraplegia Foundation) and Europe. HSP research is proceeding at a tremendous pace. At the time of the First ISHSP, HSP's molecular basis was largely unknown. In the interim, 23 additional genetic forms of HSP have been discovered and genes for 12 additional types of HSP have been identified. This has led to laboratory-based HSP diagnosis and important insights into HSP's molecular pathophysiology. We now know that HSP can result from altered axonal transport, and aberrant microtubule processing, and mitochondrial disturbance. Development of in vivo and in vitro models of HSP in the past 24 months facilitate studies of HSP's molecular pathogenesis; and permit high- throughput screening to identify potential therapeutic compounds. It is important to bring leading HSP investigators together to review major developments in HSP research; and to catalyze new research initiatives and collaborations. The Symposium objectives are to 1) develop and publish consensus understanding of clinical, genetic, pathologic, and molecular aspects of HSP; 2) utilize recent HSP gene discoveries to generate fresh insights into HSP molecular pathophysiology and treatment; 3) develop the research tools and resources necessary for HSP research including standardized diagnostic criteria, phenotype-genotype database, clinical and genetic classification, functional assessment, and surrogate markers of disease; 4) promote collaborations between investigators including sharing of research resources. By publicizing this Symposium, we will draw further attention to HSP and bring other investigators into this field. Participation of junior investigators is particularly sought. Such individuals will be invited to present abstracts during poster sessions. By consolidating and publishing information about HSP, developing research tools and shared resources, promoting collaborations, and bringing new investigators into the field, this Symposium will advance our understanding of the causes, and ultimately treatments for HSP. [unreadable] [unreadable] [unreadable]